Ignite Creation Date:
2025-12-25 @ 3:46 AM
Ignite Modification Date:
2026-02-24 @ 2:45 AM
Study NCT ID:
NCT01754402
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-02-20
First Post:
2012-11-27
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Bendamustine + Pomalidomide + Dex in R/R Multiple Myeloma
Sponsor:
Cristina Gasparetto
Organization:
Study Overview
Official Title:
A Phase I-II Study of the Combination of Bendamustine and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study is designed as a phase I-II, open label, dose finding study.
Study treatment will be as follows, in 28 day cycles:
* Pomalidomide: once daily orally (PO) dosing on days 1-21, every 28 days
* Bendamustine: once intravenously (IV) dosing on day 1, every 28 days
* Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22.
After completing 6 cycles of treatment, dexamethasone may be decreased to 20mg per investigator discretion. After completing 12 cycles of treatment, patients will proceed to the maintenance phase of the study. Patients will receive Pomalidomide on day 1-21, every 28 days and dexamethasone on days 1, 8, 15, and 22 every 28 days until time of progression.
Study treatment will be as follows, in 28 day cycles:
* Pomalidomide: once daily orally (PO) dosing on days 1-21, every 28 days
* Bendamustine: once intravenously (IV) dosing on day 1, every 28 days
* Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22.
After completing 6 cycles of treatment, dexamethasone may be decreased to 20mg per investigator discretion. After completing 12 cycles of treatment, patients will proceed to the maintenance phase of the study. Patients will receive Pomalidomide on day 1-21, every 28 days and dexamethasone on days 1, 8, 15, and 22 every 28 days until time of progression.
Detailed Description:
PRIMARY ENDPOINTS:
Phase I • Determination of the MTD of the combination therapy
Phase II:
• Response rate (CR+PR)
SECONDARY ENDPOINTS:
* Overall Response Rate (ORR)
* Progression Free Survival (PFS)
* Time to Progression (TTP)
* Time to next therapy
A total of 56 patients may be enrolled in this study: Dose escalation phase: Up to 24 subjects; Dose expansion phase: Up to a maximum of 38 patients treated at the maximum tolerated dose (MTD).
Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort. A standard 3+ 3 dose escalation schedule will be used. A minimum of 3 patients will be entered within each cohort, to be expanded to 6 patients if dose limiting toxicities (DLTs) are observed, to determine the MTD. Once the MTD is reached, any additional patients will be enrolled at the MTD level.
Dose Escalation
* Cohort -1: bendamustine 120 mg/m2; pomalidomide 2mg; dexamethasone 40mg\*\*
* Cohort 1 (initial dose): bendamustine 120/mg/m2; pomalidomide 3 mg; dexamethasone 40 mg\*\*
* Cohort 2: bendamustine 120 mg/m2; pomalidomide 4 mg; dexamethasone 40 mg\*\*
* Cohort 3: bendamustine 150 mg/m2; pomalidomide 4 mg; dexamethasone 40 mg\*\*
* Cohort 4: bendamustine 180 mg/m2; pomalidomide 4 mg; dexamethasone 40 mg\*\*
EVALUATION:
* For toxicity: 1 cycle (All patients will be considered evaluable for toxicity unless they cannot complete the first cycle of therapy due to withdrawal of consent or disease progression.)
* For efficacy: 2 cycles Intended treatment duration: Patients will continue on protocol as long as they are receiving clinical benefit and will be removed for disease progression (at the investigator's discretion the patient may be treated up to one cycle after progression noted to confirm progression), adverse event/unacceptable toxicity or side effect, or withdrawal of consent.
A DLT is defined as any of the following occurring during the first treatment cycle (28 days) that are judged by the investigator to be at least possibly related to the study therapy:
Hematologic:
* Febrile neutropenia (ANC \<1.0x109/L) with fever of 38.5 C. Subjects who enter the study with lower counts (ANC \<1.0x109/L) due to \>5030%\* marrow involvement will not be evaluated for this portion of the DLT definition.
* Grade 4 neutropenia (ANC \< 0.5x109/L) for more than 7 days despite GCSF support. Subjects who enter the study with lower counts (ANC \<1.0x109/L) due to \>5030%\* marrow involvement will not be evaluated for this portion of the DLT definition.
* Grade 4 thrombocytopenia (platelets count \<25.0x109/L) lasting \>7 days despite dose delay. Subjects who enter the study with lower counts (platelets \<50.0x109/L) due to \>5030%\* marrow involvement will not be evaluated for this portion of the DLT definition.
* Grade 3-4 thrombocytopenia associated with bleeding
* Any hematologic toxicity requiring a dose reduction within Cycle 1
* Inability to receive Day 1 dose of Cycle 2 due to drug related toxicity persisting from Cycle 1 greater than 14 days
Non-hematologic:
* Any \> Grade 3 toxicity determined by the Investigator to be related to pomalidomide or bendamustine (with the exception of thrombotic events and as noted below).
* \> Grade 3 nausea, vomiting, or diarrhea, despite the use of maximal antiemetic/antidiarrheal therapy
* \> Grade 3 neuropathy with pain
* \>Grade 3 venous thromboembolic events.
* Any Grade 4 rash related to the agents will be considered a DLT.
* A Grade 3 rash related to the agents that has not resolved to \< Grade 2 within a 10 day period despite steroids therapy will be considered a DLT.
* If an event is attributed to progressive disease, it will not be counted as a DLT.
* Any non-hematologic toxicity requiring a dose reduction within Cycle 1
* Delay in ability to receive Day 1 dose of Cycle 2 due to drug related toxicity persisting from Cycle 1 greater than 14 days
Phase I • Determination of the MTD of the combination therapy
Phase II:
• Response rate (CR+PR)
SECONDARY ENDPOINTS:
* Overall Response Rate (ORR)
* Progression Free Survival (PFS)
* Time to Progression (TTP)
* Time to next therapy
A total of 56 patients may be enrolled in this study: Dose escalation phase: Up to 24 subjects; Dose expansion phase: Up to a maximum of 38 patients treated at the maximum tolerated dose (MTD).
Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort. A standard 3+ 3 dose escalation schedule will be used. A minimum of 3 patients will be entered within each cohort, to be expanded to 6 patients if dose limiting toxicities (DLTs) are observed, to determine the MTD. Once the MTD is reached, any additional patients will be enrolled at the MTD level.
Dose Escalation
* Cohort -1: bendamustine 120 mg/m2; pomalidomide 2mg; dexamethasone 40mg\*\*
* Cohort 1 (initial dose): bendamustine 120/mg/m2; pomalidomide 3 mg; dexamethasone 40 mg\*\*
* Cohort 2: bendamustine 120 mg/m2; pomalidomide 4 mg; dexamethasone 40 mg\*\*
* Cohort 3: bendamustine 150 mg/m2; pomalidomide 4 mg; dexamethasone 40 mg\*\*
* Cohort 4: bendamustine 180 mg/m2; pomalidomide 4 mg; dexamethasone 40 mg\*\*
EVALUATION:
* For toxicity: 1 cycle (All patients will be considered evaluable for toxicity unless they cannot complete the first cycle of therapy due to withdrawal of consent or disease progression.)
* For efficacy: 2 cycles Intended treatment duration: Patients will continue on protocol as long as they are receiving clinical benefit and will be removed for disease progression (at the investigator's discretion the patient may be treated up to one cycle after progression noted to confirm progression), adverse event/unacceptable toxicity or side effect, or withdrawal of consent.
A DLT is defined as any of the following occurring during the first treatment cycle (28 days) that are judged by the investigator to be at least possibly related to the study therapy:
Hematologic:
* Febrile neutropenia (ANC \<1.0x109/L) with fever of 38.5 C. Subjects who enter the study with lower counts (ANC \<1.0x109/L) due to \>5030%\* marrow involvement will not be evaluated for this portion of the DLT definition.
* Grade 4 neutropenia (ANC \< 0.5x109/L) for more than 7 days despite GCSF support. Subjects who enter the study with lower counts (ANC \<1.0x109/L) due to \>5030%\* marrow involvement will not be evaluated for this portion of the DLT definition.
* Grade 4 thrombocytopenia (platelets count \<25.0x109/L) lasting \>7 days despite dose delay. Subjects who enter the study with lower counts (platelets \<50.0x109/L) due to \>5030%\* marrow involvement will not be evaluated for this portion of the DLT definition.
* Grade 3-4 thrombocytopenia associated with bleeding
* Any hematologic toxicity requiring a dose reduction within Cycle 1
* Inability to receive Day 1 dose of Cycle 2 due to drug related toxicity persisting from Cycle 1 greater than 14 days
Non-hematologic:
* Any \> Grade 3 toxicity determined by the Investigator to be related to pomalidomide or bendamustine (with the exception of thrombotic events and as noted below).
* \> Grade 3 nausea, vomiting, or diarrhea, despite the use of maximal antiemetic/antidiarrheal therapy
* \> Grade 3 neuropathy with pain
* \>Grade 3 venous thromboembolic events.
* Any Grade 4 rash related to the agents will be considered a DLT.
* A Grade 3 rash related to the agents that has not resolved to \< Grade 2 within a 10 day period despite steroids therapy will be considered a DLT.
* If an event is attributed to progressive disease, it will not be counted as a DLT.
* Any non-hematologic toxicity requiring a dose reduction within Cycle 1
* Delay in ability to receive Day 1 dose of Cycle 2 due to drug related toxicity persisting from Cycle 1 greater than 14 days
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| PO-MM-PI-0045 | OTHER | Celgene | View |